VELPHORO Chewable tablet Ref.[7693] Active ingredients: Sucroferric oxyhydroxide

Peritonitis, gastric and hepatic disorders and gastrointestinal surgery

Patients with a recent history of peritonitis (within the last 3 months), significant gastric or hepatic disorders and patients with major gastrointestinal surgery have not been included in clinical studies with Velphoro. Velphoro treatment should only be used in these patients following careful assessment of benefit/risk.

Discoloured stool

Sucroferric oxyhydroxide can cause discoloured (black) stool. Discoloured (black) stool may visually mask gastrointestinal bleeding (see section 4.5).

Information about sucrose and starches (carbohydrates)

Velphoro contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. It may be harmful to the teeth.

Velphoro contains potato starch and pregelatinised maize starch. Patients with diabetes should take notice that one tablet of Velphoro is equivalent to approximately 1.4 g of carbohydrates (equivalent to 0.116 bread units).

Velphoro is almost not absorbed from the gastrointestinal tract. Although the potential for interactions with medicinal products seems low, for concomitant treatment with medicinal products with a narrow therapeutic window, the clinical effect and adverse events should be monitored, on initiation or doseadjustment of either Velphoro or the concomitant medicinal product, or the physician should consider measuring blood levels. When administering any medicinal product that is already known to interact with iron (like alendronate and doxycycline) or has the potential to interact with sucroferric oxyhydroxide based only on in vitro studies like levothyroxine, the medicinal product should be administered at least one hour before or two hours after Velphoro.

In vitro studies with the following active substances did not show any relevant interaction: acetylsalicylic acid, cephalexin, cinacalcet, ciprofloxacin, clopidogrel, enalapril, hydrochlorothiazide, metformin, metoprolol, nifedipine, pioglitazone and quinidine.

Interaction studies have only been performed in healthy volunteers. They have been conducted in healthy human male and female subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Concomitant administration of Velphoro did not affect the bioavailability of these medicinal products as measured by the area under the curve (AUC).

Data from clinical studies have shown that sucroferric oxyhydroxide does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin). In addition, post-hoc analyses from clinical studies demonstrated no impact of Velphoro on iPTH lowering effect of oral Vitamin D analogues. Vitamin D and 1,25-dihydroxy Vitamin D levels remained unchanged.

Velphoro does not affect guaiac based (Haemoccult) or immunological based (iColo Rectal and Hexagon Obti) faecal occult blood tests.

Pregnancy

There are no available clinical data from the use of sucroferric oxyhydroxide on exposed human pregnancies.

Reproductive and developmental toxicity studies in animals revealed no risk with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). Sucroferric oxyhydroxide should only be used by pregnant women if clearly needed following careful assessment of benefit/risk.

Breast-feeding

There are no available clinical data from the use of Velphoro in breast-feeding women. Since absorption of iron from this medicinal product is minimal (see section 5.2), excretion of iron from sucroferric oxyhydroxide in breast milk is unlikely. A decision on whether to continue breast-feeding or to continue therapy with sucroferric oxyhydroxide should be made taking into account the benefit of breast-feeding to the child and the benefit of Velphoro therapy to the mother.

Fertility

There are no data on the effect of Velphoro on fertility in humans. In animal studies, there were no adverse effects on mating performance, fertility, and litter parameters following treatment with sucroferric oxyhydroxide (see section 5.3).

Velphoro has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The current safety profile of Velphoro is based on a total of 778 patients on haemodialysis and 57 patients on peritoneal dialysis, who received sucroferric oxyhydroxide treatment of up to 55 weeks.

In these clinical trials, approximately 43% of the patients experienced at least one adverse reaction during Velphoro treatment, and 0.36% of the adverse reactions were reported as serious. The majority of the adverse reactions reported from trials were gastrointestinal disorders, with the most frequently reported adverse reactions being diarrhoea and discoloured faeces (very common). The vast majority of these gastrointestinal disorders occurred early during treatment and abated with time with continued dosing. No dose-dependent trends were observed in the adverse reaction profile of Velphoro.

Tabulated list of adverse reactions

Adverse reactions reported from the use of Velphoro at doses from 250 mg iron/day to 3,000 mg iron/day in these patients (n=835) are listed in Table 2.

The reporting rate is classified as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100).

Table 2. Adverse reactions detected in clinical trials:

Description of selected adverse reactions

^*Diarrhoea

Diarrhoea occurred in 11.6% of patients in clinical trials. In the 55 weeks long term studies, the majority of these diarrhoea adverse reactions were transient, occurred early during treatment initiation and led to treatment discontinuation in 3.1% of the patients.

Paediatric population

In general, the safety profile of Velphoro in paediatric (2 to <18 years of age) and adult patients was comparable. The adverse reactions most frequently reported were gastrointestinal disorders including diarrhoea (very common, 16.7%), vomiting (common, 6.1%), gastritis (common, 3.0%) and discoloured faeces (common, 3.0%).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.